Melatonin most effective for sleep when taken for off-hour sleeping

Third shift, swing shift and jet-lagged travelers benefit most

Researchers from the Divisions of Sleep Medicine at Brigham and Women's Hospital and Harvard Medical School have found in a double-blind placebo-controlled clinical study, that melatonin, taken orally during non-typical sleep times, significantly improves an individual's ability to sleep.

This finding is particularly important for rotating or night-shift workers, travelers with jet lag and individuals with advanced or delayed sleep phase syndrome.

The findings appear in the May 1, 2006 issue of the journal Sleep.

Melatonin is a hormone produced by the body at night in darkness, which helps the brain determine day and night to help regulate sleep cycles and circadian timing. Retinal light exposure inhibits the release of the hormone.

Millions of Americans take melatonin supplements to improve their sleep, yet the results of prior studies on the efficacy of melatonin as a sleep-promoting agent have been mixed, according to the Agency of Healthcare Research and Quality, which carried out an extensive review of this topic two years ago. The present study, conducted at the Brigham and Women's Hospital, sought to address this question.
Thirty-six participants (21 men and 15 women), between the ages of 18 and 30 with no significant past or current medical disorders, sleep disorders, or psychological disorders were chosen for the study from a pool of applicants.

The participants refrained from alcohol, caffeine, nicotine, illicit substances and prescription and non-prescription medications for three weeks prior to the start of the study. They were studied in sound-proof suites free of time clues. Participants were first studied for three days and nights in the lab on their traditional sleep schedules to measure their normal sleep structure and melatonin production.

"Participants were then kept on a 20-hour sleep-wake schedule, simulating a traveler crossing four time zones eastward every day," explained Dr. Charles Czeisler, Chief of the Division of Sleep Medicine at Brigham and Women's Hospital and senior author of the study. "For the next three weeks, thirty minutes before each sleep episode, participants ingested either a placebo, 0.3milligrams (mg), or 5.0mg of pharmaceutical grade melatonin."

The researchers found that sleep efficiency during the six hour, 40 minute episodes was significantly higher in the groups that took melatonin during times when the body was not producing melatonin. At those times, participants taking 5.0mg of melatonin had a sleep efficiency of 83 percent and those taking 0.3mg melatonin had a sleep efficiency of 84 percent.

Sleep efficiency in both of these groups was significantly greater than that in participants taking placebo, who had a sleep efficiency of 77 percent. There was no significant difference in sleep efficiency among all participants during times when melatonin was being produced in the body.

James K. Wyatt, Ph.D., lead author of the study, Diplomate, American Board of Sleep Medicine and now acting Co-Director of the Sleep Disorders Service and Research Center at Rush University Medical Center in Chicago stated, "A landmark feature of this comprehensive research was the study of 24 successive sleep episodes in the same participants, including over 1,000 sleep recordings, across a full range if circadian phases – the body's internal 24-hour timing system. We were able to definitively show in these healthy young adults that the use of melatonin as a sleep-aid was only beneficial for sleeping when the body wasn't already releasing its own supply of melatonin."

"These data leave little doubt about the effectiveness of melatonin in alleviating sleep disturbances when attempting to sleep at the wrong time of day, at least under laboratory conditions," continued co-author Derk-Jan Dijk, now Director of the Surrey Sleep Research Centre, Surrey, England.

Czeisler concluded: "Melatonin enabled these participants to obtain an extra half hour of sleep when they attempted to do so during the day, at a time when they were not producing melatonin themselves. Melatonin did not help these young adults sleep at night, when their body was already producing melatonin. These finding have implications for millions of people who attempt to sleep at a time that is out of synch with the brain's internal clock."

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The research was supported by the National Institute on Aging, the National Institutes of Health and the National Aeronautics and Space Administration.

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By John M. Grohol, Psy.D. on
21 Feb 2009
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